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Vaccination against Streptococcus pneumoniae using truncated derivatives of polyhistidine triad protein D.

Plumptre CD, Ogunniyi AD, Paton JC - PLoS ONE (2013)

Bottom Line: In this study, we purified recombinant truncated derivatives of PhtD and examined their secondary structural composition, as well as their capacity to bind antibodies from polyclonal murine serum generated against the full length protein.This allowed the identification of a particularly immunogenic fragment of PhtD, which was also purified and characterised.These experiments revealed that whilst the immunogenic region identified may be a promising candidate to protect against sepsis, the full length PhtD was ineffective at conferring significant protective immunity.

View Article: PubMed Central - PubMed

Affiliation: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia.

ABSTRACT
Polyhistidine triad protein D (PhtD) has been described as a promising vaccine candidate for use against Streptococcus pneumoniae, but there has been a lack of examination of its structure and of which region(s) of the protein are targeted by protective immune responses. In this study, we purified recombinant truncated derivatives of PhtD and examined their secondary structural composition, as well as their capacity to bind antibodies from polyclonal murine serum generated against the full length protein. This allowed the identification of a particularly immunogenic fragment of PhtD, which was also purified and characterised. The truncated derivatives were tested as vaccine antigens in mouse models of pneumococcal sepsis and colonisation, using alum and E. coli heat labile toxin B subunit respectively as adjuvants. These experiments revealed that whilst the immunogenic region identified may be a promising candidate to protect against sepsis, the full length PhtD was ineffective at conferring significant protective immunity. These results are significant for the potential for PhtD to be used in novel vaccines, which are currently being tested in clinical trials.

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Related in: MedlinePlus

Survival times of mice challenged with P9 after immunisation with the indicated antigens.Median survival times are indicated by horizontal lines. Significant differences from the alum only control group are indicated where present (*, P<0.05; **, P<0.01).
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pone-0078916-g008: Survival times of mice challenged with P9 after immunisation with the indicated antigens.Median survival times are indicated by horizontal lines. Significant differences from the alum only control group are indicated where present (*, P<0.05; **, P<0.01).

Mentions: Lastly, the ability of PhtD and the truncated derivatives to induce protective immunity against sepsis caused by P9 was tested in a mouse model. PdT was used as a positive control immunogen, and combinations of PhtD and PdT or the PhtD adjunct and PdT were also tested to determine whether these antigens could confer additive or synergistic protection. Survival times of the mice were measured and are shown in Figure 8. Whilst marginal increases in median survival time were observed for a number of groups, only groups immunised with PhtD N1, PdT, PhtD + PdT or PhtD adjunct + PdT showed statistically significant differences compared to that of the alum group. Thus, immunisation with full length PhtD did not confer significant protective immunity. Furthermore, PhtD also did not increase the survival time of mice immunised with PhtD + PdT, compared with PdT alone. The same was true of the PhtD adjunct in combination with PdT. Antibody titre measurements (shown in Table 4) from pre-challenge pooled sera demonstrated that, despite the lack of protection, strong IgG responses had been induced, especially for the PhtD adjunct. It was therefore concluded that PhtD is a suboptimal candidate for a protein vaccine component in this model of pneumococcal disease, relative to PdT.


Vaccination against Streptococcus pneumoniae using truncated derivatives of polyhistidine triad protein D.

Plumptre CD, Ogunniyi AD, Paton JC - PLoS ONE (2013)

Survival times of mice challenged with P9 after immunisation with the indicated antigens.Median survival times are indicated by horizontal lines. Significant differences from the alum only control group are indicated where present (*, P<0.05; **, P<0.01).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3814962&req=5

pone-0078916-g008: Survival times of mice challenged with P9 after immunisation with the indicated antigens.Median survival times are indicated by horizontal lines. Significant differences from the alum only control group are indicated where present (*, P<0.05; **, P<0.01).
Mentions: Lastly, the ability of PhtD and the truncated derivatives to induce protective immunity against sepsis caused by P9 was tested in a mouse model. PdT was used as a positive control immunogen, and combinations of PhtD and PdT or the PhtD adjunct and PdT were also tested to determine whether these antigens could confer additive or synergistic protection. Survival times of the mice were measured and are shown in Figure 8. Whilst marginal increases in median survival time were observed for a number of groups, only groups immunised with PhtD N1, PdT, PhtD + PdT or PhtD adjunct + PdT showed statistically significant differences compared to that of the alum group. Thus, immunisation with full length PhtD did not confer significant protective immunity. Furthermore, PhtD also did not increase the survival time of mice immunised with PhtD + PdT, compared with PdT alone. The same was true of the PhtD adjunct in combination with PdT. Antibody titre measurements (shown in Table 4) from pre-challenge pooled sera demonstrated that, despite the lack of protection, strong IgG responses had been induced, especially for the PhtD adjunct. It was therefore concluded that PhtD is a suboptimal candidate for a protein vaccine component in this model of pneumococcal disease, relative to PdT.

Bottom Line: In this study, we purified recombinant truncated derivatives of PhtD and examined their secondary structural composition, as well as their capacity to bind antibodies from polyclonal murine serum generated against the full length protein.This allowed the identification of a particularly immunogenic fragment of PhtD, which was also purified and characterised.These experiments revealed that whilst the immunogenic region identified may be a promising candidate to protect against sepsis, the full length PhtD was ineffective at conferring significant protective immunity.

View Article: PubMed Central - PubMed

Affiliation: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia.

ABSTRACT
Polyhistidine triad protein D (PhtD) has been described as a promising vaccine candidate for use against Streptococcus pneumoniae, but there has been a lack of examination of its structure and of which region(s) of the protein are targeted by protective immune responses. In this study, we purified recombinant truncated derivatives of PhtD and examined their secondary structural composition, as well as their capacity to bind antibodies from polyclonal murine serum generated against the full length protein. This allowed the identification of a particularly immunogenic fragment of PhtD, which was also purified and characterised. The truncated derivatives were tested as vaccine antigens in mouse models of pneumococcal sepsis and colonisation, using alum and E. coli heat labile toxin B subunit respectively as adjuvants. These experiments revealed that whilst the immunogenic region identified may be a promising candidate to protect against sepsis, the full length PhtD was ineffective at conferring significant protective immunity. These results are significant for the potential for PhtD to be used in novel vaccines, which are currently being tested in clinical trials.

Show MeSH
Related in: MedlinePlus